The objectives of the proposed research are to elucidate the functional roles of cyclic GMP-dependent protein kinase (G-PK) and its stimulatory modulator in normal and malignant cell proliferation. The experimental models to be employed are: the Morris hepatoma 3294A (vs. normal liver), the mitogen-stimulated lymphocytes (vs. non-stimulated cells) and the adenovirus (type 2)-infected human KB cells (vs. non-infected cells). Attempts will be made to seek, characterize or identify possible changes in patterns, localizations and properties or species of G-PK and its stimulatory modulator, as well as those of endogenous substrate proteins of G-PK, in cells undergoing proliferation. The above parameters will be compared to those obtained for cyclic AMP-dependent protein kinase (A-PK) and its inhibitory modulator (protein inhibitor). It is hoped that the proposed studies would shed light on roles of G-PK and A-PK, presumably the physiologic target enzymes for cyclic GMP and cyclic AMP, respectively, in the process or regulation of cell proliferation.